DRUCKEN

Lymphoma, Leukemia & HSCT

The UCT Mainz Program in Hematologic Malignancies is focusing on an efficient transfer of innovative findings in basic science into novel therapeutic strategies. As the sole certified transplantation center in Rhineland-Palatinate, we performed 179 hemopoietic stem cell transplants (HSCT) including 117 allogeneic HSCTs in 2018.

Clinical Research

Within our clinical research program, we performed 327 clinical trials including 33 phase I studies and enrolled 1,814 patients. Investigators of the UCT Mainz Program Hematologic Malignancies substantially contributed to pivotal national and international studies such as the analysis of Blinatumomab in non-Hodgkin lymphoma (Hess G., et al. JCO. 2016), the CASTOR trial in multiple myeloma (Munder M., et al. NEJM. 2016), Midostaurin in AML (Kindler T., et al. Blood. 2019).  

Translational Projects

Translational research within the program addresses cancer immunotherapy, leukemogenesis and genetic instability. Within the previous funding period a new DFG-funded Emmy-Noether group (M. Kühn) and a DKTK young investigator group (B. Guezguez) have been established. Further achievements include i) development of a unique transcutaneous vaccination method currently tested in an IIT (Radsak MP. Eur. J Immunol. 2019; patent: EP 18204287.9; see also B 2.); ii) identification of mechanisms of immune evasion during disease progression (Schrörs B., et al. Oncotarget. 2017), iii) generation of natural cytotoxicity receptor (NCR)-based CARs directed against AML cells for adoptive cellular immunotherapy (patent: EP 19180008.5) or v) identification of aberrant NCAM (CD56) expression as resistance marker and novel target in AML (Sasca D., et al. Blood. 2019). Current efforts aim at transferring our findings in basic research into investigator initiated, hypothesis-driven clinical trials.

Most significant publications since 2015

  • Sasca D., Szybinski J., Schuler A., Shah V., Heidelberger J., Haehnel P.S., Dolnik A., Kriege O., Fehr E.M., Gebhardt W.H., Reid G., Scholl C., Theobald M., Bullinger L., Beli P., Kindler T. 2019. NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML. Blood. 133, 2305-2319.
  • Schlenk R.F., Weber D., Fiedler W., Salih H.R., Wulf G., Salwender H., Schroeder T., Kindler T., Lubbert M., Wolf D., Westermann J., Kraemer D., Gotze K.S., Horst H.A., Krauter J., Girschikofsky M., Ringhoffer M., Sudhoff T., Held G., Derigs H.G., Schroers R., Greil R., Griesshammer M., Lange E., Burchardt A., Martens U., Hertenstein B., Marretta L., Heuser M., Thol F., Gaidzik V.I., Herr W., Krzykalla J., Benner A., Dohner K., Ganser A., Paschka P., Dohner H. 2019. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood. 133, 840-851.
  • Bialojan A., Sohl J., Rausch J., Aranda Lopez P., Denny M., Langguth P., Hartmann A.K., Yagita H., Probst H.C., Schild H., Radsak M.P. 2019. Transcutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in mice. European journal of immunology. 49(11):2083-2094.
  • Schrörs B., Lübcke S., Lennerz V., Fatho M., Bicker A., Wölfel C., Derigs P., Hankeln T., Schadendorf D., Paschen A., Wölfel T. 2017. HLA class I loss in metachronous metastases prevents continuous T cell recognition of mutated neoantigens in a human melanoma model. Oncotarget. 8(17):28312-28327.
  • Palumbo A., Chanan-Khan A., Weisel K., Nooka A.K., Masszi T., Beksac M., Spicka I., Hungria V., Munder M., Mateos M.V., Mark T.M., Qi M., Schecter J., Amin H., Qin X., Deraedt W., Ahmadi T., Spencer A., Sonneveld P., CASTOR Investigators. 2016. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 375(8):754-66.
  • Goebeler M.E., Knop S., Viardot A., Kufer P., Topp M.S., Einsele H., Noppeney R., Hess G., Kallert S., Mackensen A., Rupertus K., Kanz L., Libicher M., Nagorsen D., Zugmaier G., Klinger M., Wolf A., Dorsch B., Quednau B.D., Schmidt M., Scheele J., Baeuerle P.A., Leo E., Bargou R.C. 2016. Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study. J Clin Oncol. 34(10):1104-11.
  • Distler E., Albrecht J., Brunk A., Khan S., Schnürer E., Frey M., Mottok A., Jordán-Garrote A.L., Brede C., Beilhack A., Mades A., Tomsitz D., Theobald M., Herr W., Hartwig U.F. 2016. Patient-individualized CD8(+) cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice. Int J Cancer. 138(5):1256-68.
     
  • Hess G., Keller U., Scholz C.W., Witzens-Harig M., Atta J., Buske C., Kirschey S., Ruckes C., Medler C., van Oordt C., Klapper W., Theobald M., Dreyling M. 2015. Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma. Leukemia. 29(8):1695-701.
     
  • Kirschey S., Flohr T., Wolf H.H., Frickhofen N., Gramatzki M., Link H., Basara N., Peter N., Meyer R.G., Schmitz N., Weidmann E., Banat A., Schulz A., Kolbe K., Derigs G., Theobald M., Hess G. 2015. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 168(6):824-34.
     
  • Mai E.K., Bertsch U., Dürig J., Kunz C., Haenel M., Blau I.W., Munder M., Jauch A., Schurich B., Hielscher T., Merz M., Huegle-Doerr B., Seckinger A., Hose D., Hillengass J., Raab M.S., Neben K., Lindemann H.W., Zeis M., Gerecke C., Schmidt-Wolf I.G., Weisel K., Scheid C., Salwender H., Goldschmidt H. 2015. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 29(8):1721-9.
     
  • O'Connor O.A., Horwitz S., Masszi T., Van Hoof A., Brown P., Doorduijn J., Hess G., Jurczak W., Knoblauch P., Chawla C., Bhat G., Choi M.R., Walewski J., Savage K., Foss F., Allen L.F., Shustov A. 2015. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 33(23):2492-9.
     
  • Zupke O., Distler E., Jürchott A., Paiphansiri U., Dass M., Thomas S., Hartwig U.F., Theobald M., Landfester K., Mailänder V., Herr W. 2015. Nanoparticles and antigen-specific T-cell therapeutics: a comprehensive study on uptake and release. Nanomedicine (Lond). 10(7):1063-76.